1566 Cough Suppressants Expectorants Mucolytics and Nasal Decongestants

Naphoptic-A; Ocuhist; Opcon-A; VasoClear A; VasoClear†; Vasocon-A; Vi- Profile Noscapine Hydrochloride (BANM, rINNM) sine-A; Venez.: Camolyn Plus; Fesanol†; Pinazo; Soltin; Soluclear. Nicocodine is an opioid related to codeine (p.37). It has been Used as an adjunct in: Fr.: Xylocaine; Spain: Anestesico. used as the hydrochloride for its central cough suppressant ef- Hidrocloruro de noscapina; Narcotine Hydrochloride; Noscap- fects in non-productive cough (p.1547). Nicocodine hydrochlo- ine, chlorhydrate de; Noscapini hydrochloridum; Noscapini Hy- ride is given orally in doses of 5 to 7.5 mg up to three times daily. drochloridum Monohydricum; Noscapinium Chloride; Noskapi- inihydrokloridi; Noskapin hydrochlorid monohydrát; Noskapin- Neltenexine (rINN) Preparations hydroklorid; Noskapino hidrochloridas; Noskapiny chlorowo- Neltenexina; Nelténexine; Neltenexinum. 4′,6′-Dibromo-α- Proprietary Preparations (details are given in Part 3) dorek; Noszkapin-hidroklorid. [(trans-4-hydroxycyclohexyl)amino]-2-thiophene-carboxy-o- Austria: Tusscodin. toluidide. Носкапина Гидрохлорид Нелтенексин C22H23NO7,HCl,H2O = 467.9. CAS — 912-60-7 (anhydrous noscapine hydrochloride). C18H20Br2N2O2S = 488.2. Normethadone Hydrochloride (BANM, rINNM) CAS — 99453-84-6. ATC — R05DA07. ATC — R05CB14. Desmethylmethadone Hydrochloride; Hidrocloruro de ATC Vet — QR05DA07. normetadona; Hoechst-10582 (normethadone); Normétha- ATC Vet — QR05CB14. Pharmacopoeias. In Eur. (see p.vii) and Int. (both with H O); done, Chlorhydrate de; Normethadoni Hydrochloridum; Phe- 2 in Jpn (with xH2O). nyldimazone Hydrochloride. 6-Dimethylamino-4,4-diphenylhex- Ph. Eur. 6.2 (Noscapine Hydrochloride). A white or almost Br an-3-one hydrochloride. white, hygroscopic, crystalline powder or colourless crystals. Норметадона Гидрохлорид Freely soluble in water and in alcohol. Aqueous solutions are C20H25NO,HCl = 331.9. faintly acid; the base may be precipitated when the solutions are Br CAS — 467-85-6 (normethadone); 847-84-7 (normetha- allowed to stand. A 2% solution in water has a pH of not less than done hydrochloride). 3.0. Protect from light. ATC — R05DA06. HN NH Adverse Effects and Precautions ATC Vet — QR05DA06. As for Dextromethorphan, p.1555. Hypersensitivity reactions O H OH have been reported. S CH3 Breast feeding. Maximum concentrations of noscapine in the H breast milk of 8 women given 100 or 150 mg of noscapine N ranged1 from 11 to 83 nanograms/mL. It was estimated that CH3 breast-fed infants of mothers receiving noscapine 50 mg three Profile times daily would ingest at most 300 nanograms/kg of noscap- Neltenexine is a mucolytic that has been used in respiratory dis- CH3 ine, an amount considered unlikely to be a hazard. No adverse orders associated with productive cough (p.1547). It has been O effects have been seen in breast-fed infants whose mothers were given orally as the monohydrate, in usual doses of 37.4 mg three given noscapine, and the American Academy of Pediatrics2 con- siders that it is therefore usually compatible with breast feeding. times daily. Neltenexine has also been given rectally as the hy- (normethadone) drochloride. 1. Olsson B, et al. Excretion of noscapine in human breast milk. Preparations Eur J Clin Pharmacol 1986; 30: 213–15. Profile 2. American Academy of Pediatrics. The transfer of drugs and oth- Proprietary Preparations (details are given in Part 3) Normethadone is closely related to methadone (p.82). The hy- er chemicals into human milk. Pediatrics 2001; 108: 776–89. Ital.: Alveoten; Muco4; Tenoxol. drochloride is given orally as a cough suppressant in preparations Correction. ibid.; 1029. Also available at: for non-productive cough. http://aappolicy.aappublications.org/cgi/content/full/ pediatrics%3b108/3/776 (accessed 13/12/06) Preparations Nepinalone (rINN) Pregnancy. The UK CSM stood by their recommendation1 that Proprietary Preparations (details are given in Part 3) Nepinalona; Népinalone; Nepinalonum. (±)-3,4-Dihydro-1-me- products containing noscapine should be contra-indicated in Multi-ingredient: Canad.: Cophylac. women of child-bearing potential (because of potential mutagen- thyl-1-(2-piperidinoethyl)-2(1H)-napthalenone. ic effects2), after criticism that the decision was based solely on Непиналон the results of in-vitro work.3 C H NO = 271.4. 18 25 Noscapine (BAN, rINN) 1. Asscher AW, Fowler LK. Papaveretum in women of childbear- CAS — 22443-11-4. ing potential. BMJ 1991; 303: 648. ATC — R05DB26. Narcotine; L-α-Narcotine; Noscapina; Noscapinum; Noskapiini; 2. Committee on Safety of Medicines. Genotoxicity of papaveretum ATC Vet — QR05DB26. Noskapin; Noskapinas; Noszkapin; NSC-5366. (3S)-6,7-Dimeth- and noscapine. Current Problems 31 1991. Also available at: http:// oxy-3-[(5R)-5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxo- www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE& dDocName=CON2024449&RevisionSelectionMethod= lo[4,5-g]isoquinolin-5-yl]phthalide. LatestReleased (accessed 21/03/07) Носкапин 3. Allen S, et al. Papaveretum in women of child bearing potential. BMJ 1991; 303: 647. C22H23NO7 = 413.4. N CAS — 128-62-1. Interactions ATC — R05DA07. Noscapine should not be given with alcohol or other CNS de- ATC Vet — QR05DA07. pressants. CH3 O Anticoagulants. For mention of a possible interaction between O noscapine and warfarin, see Cough Suppressants, p.1430. Pharmacokinetics N O ◊ References. CH3 Profile H H 1. Karlsson MO, et al. Pharmacokinetics of oral noscapine. Eur J Nepinalone has been used as the hydrochloride as a cough sup- H3CO Clin Pharmacol 1990; 39: 275–9. pressant in non-productive cough (p.1547). Oral doses of nepi- O 2. Karlsson MO, Dahlstrom B. Serum protein binding of noscap- ine: influence of a reversible hydrolysis. J Pharm Pharmacol nalone hydrochloride 10 mg have been given three times daily. 1990; 42: 140–3. Preparations O Uses and Administration Proprietary Preparations (details are given in Part 3) H3CO OCH Noscapine is a centrally acting cough suppressant that has ac- Ital.: Nepituss; Placatus; Tussolvina. 3 tions and uses similar to those of dextromethorphan (p.1556). It is given in an oral dose of up to 50 mg three times daily. It is also Description. Noscapine is an alkaloid obtained from opium. used rectally. Noscapine has also been given as the ascorbate, Nicocodine (BAN, rINN) Pharmacopoeias. In Chin., Eur. (see p.vii), Int., Jpn, and US. camsilate, embonate, and the hydrochloride. Ph. Eur. 6.2 (Noscapine). A white or almost white, crystalline Nicocodina; Nicocodinum. 6-Nicotinoylcodeine; 3-O-Methyl-6- powder or colourless crystals. Practically insoluble in water at Preparations O-nicotinoylmorphine. 20°, very slightly soluble at 100°; slightly soluble in alcohol; sol- Proprietary Preparations (details are given in Part 3) Никокодин uble in acetone; dissolves in strong acids although the base may Belg.: Nosca-Mereprine; Noscaflex; Chile: Factoss†; Ger.: Capval; Hong Kong: Recoma; Indon.: Longatin; Mercotin; Neth.: Roter Noscapect; C24H24N2O4 = 404.5. be precipitated on dilution with water. Protect from light. CAS — 3688-66-2. Streptuss kriebelhoest†; S.Afr.: Nitepax; Spain: Tuscalman; Swed.: Nipax- USP 31 (Noscapine). A fine, white or practically white, crystal- on; Switz.: Tussanil N. line powder. Practically insoluble in water; slightly soluble in al- Multi-ingredient: Arg.: Funciobron; Graneodin N; Jarabe Bago†; No-Tos cohol and in ether; soluble in acetone; freely soluble in chloro- Pocket; Saltos Infantil†; Saltos†; Tosedrin Compuesto; Vi-Balsabron†; Aus- O form. tria: Pneumopect; Tuscalman; Belg.: Noscaflex; Rosils†; Braz.: Expec- H3C tussin†; Ipecol†; Chile: AB Antitusivo; Captus; Congestex; Cotibin Flu†; Freshmel Tos; Graneodin N†; Graneodin-Tos; Gripexin Limonada Caliente; Noscapine Camsilate (BANM, rINNM) Gripexin Nueva Formula Compuesto†; Kitadol Flu Noche†; Kitadol Flu†; Pectoserum†; Tapsin Compuesto; Tapsin Compuesto con Clorfenamina; O Camphoscapine; Camsilato de noscapina; Noscapine, Camsilate de; Noscapine Camsylate; Noscapini Camsilas. Noscapine cam- Tapsin Compuesto Dia/Noche Plus; Tapsin Compuesto DN; Tapsin H Limonada D.N.†; Tapsin Limonada Dia†; Tapsin Limonada Noche†; Fin.: O N phor-10-sulphonate. Codesan N†; Posivil†; Fr.: Tussisedal; Hong Kong: Asmeton; Coldcap-A; H H Носкапина Камзилат Coldrex†; Coldtab-2; Mefedra-N†; Panadol Cold & Flu Extra; India: Co- CH3 scopin; Coscopin Plus; Indon.: Flunadin; Noscapax; Paratusin; Tilomix; N O C22H23NO7, C10H16O4S = 645.7. Swed.: Spasmofen; Switz.: Brosoline-Rectocaps†; DemoTussil; Hederix; CAS — 25333-79-3. Noscorex; Spasmosol; Tossamine; Tossamine plus; Tuscalman; Tussanil ATC — R05DA07. Compositum†; Thai.: Asmeton†; Turk.: Coldeks. ATC Vet — QR05DA07.